COH29
(Synonyms: RNR Inhibitor COH29) 目录号 : GC19110
COH29 (RNR Inhibitor COH29) 是一种有效的核糖核苷酸还原酶 (RNR) 抑制剂，具有抗癌活性。 COH29 抑制 RNR 的 α 和 β 亚基，IC50 为 16 μM。
Cas No.:1190932-38-7
Sample solution is provided at 25 µL, 10mM.
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COH29 is a potent ribonucleotide reductase (RNR) inhibitor with anticancer activity. COH29 inhibits α and β subunit of RNR with IC50s of 16 uM.
COH29 overcome hydroxyurea and gemcitabine resistance in cancer cells. It effectively inhibits proliferation of most cell lines in the NCI 60 human cancer panel, most notably ovarian cancer and leukemia, but exerts little effect on normal fibroblasts or endothelial cells. Site-directed mutagenesis, NMR and surface plasmon resonance biosensor studies confirm COH29 binding to the proposed ligand-binding pocket and offer evidence for assembly blockade of the RRM1-RRM2 quaternary structure[1].
COH29 results in a dose-dependent inhibition of MOLT-4 tumor xenograft growth with twice-daily oral dosing at 50 mg/kg and 100 mg/kg, which is pronounced by Day 12 of treatment. Similarly, 7 days of treatment of mice bearing TOV11D xenografts with 200, 300, or 400 mg/kg/day COH29 results in a dose-dependent inhibition of tumor xenograft growth. Tumor growth is significantly inhibited compared with the control group[1].
References:
[1]. Zhou B, et al. A small-molecule blocking ribonucleotide reductase holoenzyme formation inhibits cancer cell growth and overcomes drug resistance.Cancer Res. 2013 Nov 1;73(21):6484-93.
[2]. Chen MC, et al. The Novel Ribonucleotide Reductase Inhibitor COH29 Inhibits DNA Repair In Vitro. Mol Pharmacol. 2015 Jun;87(6):996-1005.
Cell experiment: | Cells is seeded into 96-well plates in 100 µL of complete medium at 2000 to 5000 cells per well, depending on the cell line’s growth rate. After overnight incubation, test compound is added to each well at various concentrations in 50 µL of culture medium. After a further incubation for 96 hours at 37°C, fluorescein diacetate (final concentration: 10 mg/mL) and eosin Y [final concentration: 0.1% (w/v)] is added to each well, and the cells is incubated for an additional 20 minutes at 37°C. Cytotoxicity is assessed by Digital Imaging Microscopy System detection Viability is assessed using MTS [(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)] as previously described[1]. |
Animal experiment: | Female NSG mice (NOD/SCID/IL2Rgamma null) aged 8-10 weeks are supplied. Each mouse is injected with 5×106Molt-4 or TOV-112D cells subcutaneously in the right flank, and tumor volume is monitored (0.5×l×w2). After the tumors reach approximately 70 mm3, COH29 in 30% solutol is administered daily by gavage in a one or two dose schedule. Mice is sacrificed on the 28th day after cancer cell transplantation[1]. |
References: [1]. Zhou B, et al. A small-molecule blocking ribonucleotide reductase holoenzyme formation inhibits cancer cell growth and overcomes drug resistance.Cancer Res. 2013 Nov 1;73(21):6484-93. | |
| Cas No. | 1190932-38-7 | SDF | |
| 别名 | RNR Inhibitor COH29 | ||
| Canonical SMILES | O=C(NC1=NC(C2=CC=C(O)C(O)=C2)=C(C3=CC=CC=C3)S1)C4=CC=C(O)C(O)=C4 | ||
| 分子式 | C22H16N2O5S | 分子量 | 420.44 |
| 溶解度 | DMSO : ≥ 31 mg/mL (73.73 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3785 mL | 11.8923 mL | 23.7846 mL |
| 5 mM | 0.4757 mL | 2.3785 mL | 4.7569 mL |
| 10 mM | 0.2378 mL | 1.1892 mL | 2.3785 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet